Artificial intelligence tools for molecular analysis of sensitization profiles in patients with atopic dermatitis and bronchial asthma

Background. The variety of characteristics that should be taken into account in the clinical phenotyping of allergic diseases is currently being discussed. One of such characteristics is the individual spectrum of sensitization. An important stage in modern allergology has become the introduction of molecules / components for the detection of mediated reactions to specific class E immunoglobulins.

Aim. To determine the dominant phenotypes of sensitization in patients with severe atopic dermatitis and bronchial asthma based on the results of molecular diagnostics by the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) method using machine learning.

Materials and methods. The study included 100 patients who were candidates for genetically engineered biological therapy (n = 63), severe atopic dermatitis (n = 20), or their combination (n = 17) were included. Allergodiagnosis was performed by the ImmunoCAP ISAC method.

Results. Based on the results of the study, 6 phenotypes were identified. In phenotype 1, pollen molecules (Amb a1, Phl p4) and crossed reactive food molecules (Mal d1, Ara h8, Gly m4, Act d8, Pru p3) are the leading, among epidermal molecules only Fel d1 (epidermal allergen) and Asp f6 (fungal allergen) are found. For phenotype 2, the significant allergens were fungal (Asp f6), epidermal (Can f1, Can f5, Can f6, Fel d1), food (Gad c1) and cross reactive food molecules (Mal d1, Pru p1. Ara h8, Cor a1.0401). In phenotype 4, only 3 allergen groups are present:

epidermal (Fel d1, Fel d2, Can f5, Can f6, Can f3), fungal (Asp f6), and cross food allergy (Jug r3, Pru p3). Phenotype 5 and 6 are dominated by epidermal molecules (Can f1 and Fel d1), true food allergies allergens (Gad c1 and Gal d1 and Gad c1, Gal d1, Gal d3, respectively). In phenotype 3, a combination of the previously labeled molecules is noted.

Conclusion. Each of the identified phenotypes reveals a different set of molecules that can be used in real clinical practice to develop reduced panels, making them more accessible.

1. Paller A.S., Spergel J.M., Mina-Osorio P., Irvine A.D. The atopic march and atopic multimorbidity: many trajectories, many pathways. J Allergy Clin Immunol 2019;143(1):46–55. DOI: 10.1016/j.jaci.2018.11.006

2. Mersha T.B., Hershey K., Gurjit K. Precision medicine in allergic disorders. In: Middleton’s allergy: principles and practice. 9th ed., vol. 2. New York: Elsevier, 2020. Pp. 1441–1450.

3. Valenta R., Duchene M., Vrtala S. et al. Recombinant allergens for immunoblot diagnosis of tree-pollen allergy. J Allergy Clin Immunol 1991;88(6):889–94. DOI:10.1016/0091-6749(91)90245-J

4. van Hage M., Hamsten C., Valenta R. ImmunoCAP assays: pros and cons in allergology. J Allergy Clin Immunol 2017;140(4):974–7. DOI: 10.1016/j.jaci.2017.05.008

5. Vaňková R., Čelakovská J., Bukač J. et al. Sensitization to molecular components in 104 atopic dermatitis patients in relation to subgroups of patients suffering from bronchial asthma and allergic rhinitis. Acta Medica (Hradec Kralove) 2020;63(4):164–75. DOI: 10.14712/18059694.2020.59

6. Venkatesan P. 2023 GINA report for asthma. Lancet Respir Med 2023;11(7):589. DOI: 10.1016/S2213-2600(23)00230-8

7. Atopicheskij dermatit. Proekt klinicheskih rekomendacij. 2020 g. RAAKI. URL: https://raaci.ru/dat/pdf/KR/atopic_dermatitis_2020.pdf?ysclid=li7geerqe3115604531 .

8. Ackermann M.R., Blömer J., Kuntze D., Sohler C. Analysis of agglomerative clustering. Algorithmica 2010;69(1):184–215. DOI:10.1007/s00453-012-9717-4

9. Ščevková J., Vašková Z., Sepšiová R. et al. Relationship between Poaceae pollen and Phl p 5 allergen concentrations and the impact of weather variables and air pollutants on their levels in the atmosphere. Heliyon 2020;6(7):e04421. DOI: 10.1016/j.heliyon.2020.e04421

10. Čelakovská J., Bukač J., Cermákova E. et al. Analysis of results of specific IgE in 100 atopic dermatitis patients with the use of multiplex examination ALEX2-Allergy Explorer. Int J Mol Sci 2021;22(10):5286. DOI: 10.3390/IJMS22105286

11. Scala E., Abeni D., Guerra E.C. et al. β-1,3-glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area. Clin Exp Allergy 2020;50(4):487–98. DOI: 10.1111/cea.13555

12. Gaitanis G., Magiatis P., Hantschke M. et al. The Malassezia genus in skin and systemic diseases. Clin Microbiol Rev 2012;25(1):106–41. DOI: 10.1128/CMR.00021-11

13. Ott H., Fölster-Holst R., Merk H.F. et al. Allergen microarrays: a novel tool for high-resolution IgE profiling in adults with atopic dermatitis. Eur J Dermatol 2010;20(1):54–61. DOI: 10.1684/ejd.2010.0810

14. Aglas L., Soh W.T., Kraiem A. et al. Ligand binding of PR-10 proteins with a particular focus on the Bet v 1 allergen family. Curr Allergy Asthma Rep 2020;20(7):25. DOI: 10.1007/s11882-020-00918-4

15. Biedermann T., Winther L., Till S.J. et al. Birch pollen allergy in Europe. Allergy 2019;74(7):1237–48. DOI: 10.1111/all.13758

16. Iweala O.I., Choudhary S.K., Commins S.P. Food allergy. Curr Gastroenterol Rep 2018;20(5):17. DOI: 10.1007/s11894-018-0624-y

17. Warren C.M., Jiang J., Gupta R.S. Epidemiology and burden of food allergy. Curr Allergy Asthma Rep 2020;20(2):6. DOI: 10.1007/s11882-020-0898-7

18. Nilsson O.B., Binnmyr J., Zoltowska A. et al. Characterization of the dog lipocalin allergen Can f 6: the role in cross-reactivity with cat and horse. Allergy 2012;67(6):751–7. DOI: 10.1111/j.1398-9995.2012.02826.x

19. Niespodziana K., Focke-Tejkl M., Linhart B. et al. A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS. J Allergy Clin Immunol. 2011;127(6):1562–70.e6. DOI:10.1016/j.jaci.2011.02.004

20. Barradas Lopes J., Labrador-Horrilo M., Bartolomé B., Cunha L. The role of molecular allergens in the diagnosis of cat-pork syndrome: an unusual case report. Acta Med Port 2022;35(5):388–91. DOI: 10.20344/amp.15483

21. Čelakovská J., Ettlerová K., Ettler K. et al. Sensitization to aeroallergens in atopic dermatitis patients: association with concomitant allergic diseases. J Eur Acad Dermatol Venereol 2015;29(8):1500–5. DOI: 10.1111/jdv.12891

22. Nordlund B., Konradsen J.R., Kull I. et al. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy 2012;67(5):661–9. DOI: 10.1111/j.1398-9995.2012.02797.x

23. Pónyai G., Hidvégi B., Németh I. et al. Contact and aeroallergens in adulthood atopic dermatitis. J Eur Acad Dermatol Venereol 2008;22(11):1346–55. DOI: 10.1111/j.1468-3083.2008.02886.x

24. Muthu V., Sehgal I.S., Dhooria S. et al. Utility of recombinant Aspergillus fumigatus antigens in the diagnosis of allergic bronchopulmonary aspergillosis: a systematic review and diagnostic test accuracy meta-analysis. Clin Exp Allergy 2018;48(9):1107–36. DOI: 10.1111/cea.13216

25. Wojciechowska M., Żbikowska-Gotz M., Marek-Józefowicz L. et al. Allergic phenotypes in adult patients with atopic dermatitis, determined with the ISAC test (ImmunoCAP ISAC). Postepy Dermatol Alergol 2018;35(4):351–9. DOI: 10.5114/ada.2018.77664